Mapping the Neurobiological Risks and Consequences of Alcohol Use in Adolescence and Across the Lifespan

项目摘要/摘要 在全球范围内，13.4亿人消费有害数量的酒精，其中酒精使用占178万 2020年的死亡人数。在整个青春期，酒精的使用经常开始，并明显升级。发病率： 酒精使用障碍(AUD)和相关症状遵循类似的模式，在以下年龄达到顶峰 18年和20年。因此，AUD被描述为一种青壮年的“发育障碍”。而当 问题饮酒率在年轻人中最高，近年来 老年人中有问题的饮酒，与AUD和酒精相关的相应增加 住院治疗。长期以来，导致酒精使用障碍(AUD)的发育过程 认识到，但在我们对神经生物学预测因素的认识上仍然存在很大差距 AUD过程中的“里程碑”，以及贯穿始终的酒精使用对神经生物学的影响 青春期进入中年和老年。因此，我们的首要目标是发现神经生物学 青少年饮酒的风险，并将其与青少年饮酒的后果区分开来 青春期和整个生命周期。这将在一个发展框架内进行，并与 注重可复制性和严格的因果模型。为了实现我们的目标，我们需要大规模的纵向 对酒精使用的评估，捕捉青少年风险的高峰期，并纳入综合 其他物质使用、行为、环境和成像数据。来自青少年大脑的数据和 因此，认知发展(ABCD)研究提供了一个前所未有的机会来解决我们的目标。至 将我们对饮酒后果的研究延伸到整个生命周期，我们将结合(或协调) Xian chu ju数据使用来自不同生命阶段的大规模、高质量队列数据，并联合分析这些数据以 建立一生中关键时期饮酒的神经生物学预测因子和后果 在一个统一的框架内。该项目代表了以下方面的创新：1)以发展的方式 酒精使用和神经生物学之间的关系，这一研究的重点是青春期，但也延伸到 寿命到成年；2)在寿命内协调四个里程碑式的数据集的数据；3) 注重促进因果推理的方法严谨性；4)神经成像和 研究团队独有的生物统计学技术；以及(5)注重可复制性和开放科学 框架，包括所有分析和公开可用的代码的预注册。该项目的成果将 有可能为药物开发提供新的神经生物学靶点，以及酒精 由神经科学提供信息的预防和干预。我们还将采取第一步，以实现 建立一个更大的国际纵向队列研究联盟，重点研究酒精的影响 终生使用对大脑健康有帮助。

PROJECT SUMMARY/ABSTRACT Globally, 1.34 billion people consume alcohol in harmful amounts, with alcohol use accounting for 1.78 million deaths in 2020. Alcohol use often begins, and noticeably escalates, throughout adolescence. Incidence of alcohol use disorder (AUD) and related symptomatology follows a similar pattern, peaking between the ages of 18 and 20 years. As such, AUD has been described as a “developmental disorder” of young adulthood. While rates of problematic drinking are highest among young adults, recent years have seen large increases in problematic drinking among older adults, with corresponding increases in AUD and alcohol-related hospitalizations. The developmental processes contributing to alcohol use disorders (AUD) have long been recognised but there remain substantial gaps in our knowledge about the neurobiological predictors of “milestones” along the pathway to AUD, as well as the neurobiological consequences of alcohol use throughout adolescence into midlife and older age. Our overarching aim is to therefore uncover the neurobiological risks of adolescent alcohol use and distinguish these from the consequences of alcohol use in adolescence and across the lifespan. This will be done within a developmental framework and conducted with a focus on replicability and rigorous causal modelling. To address our aim, we need large-scale longitudinal assessments of alcohol use, capturing the peak period of adolescent risk, and incorporating comprehensive other substance use, behavioral, environmental, and imaging data. Data from the Adolescent Brain and Cognitive Development (ABCD) Study therefore provide an unprecedented opportunity to address our aim. To extend our examination of the consequences of alcohol use across the lifespan, we will combine (or harmonize) ABCD data with large-scale, high quality cohort data from different life stages and jointly analyze these data to establish the neurobiological predictors and consequences of alcohol use at key periods across the lifespan within a unified framework. This project represents innovation in its: 1) developmental approach to the relationship between alcohol use and neurobiology which focuses on adolescence but also extends across the lifespan into older adulthood; 2) harmonization of data across four landmark datasets across the lifespan; 3) methodological rigor focusing on the promotion of causal inference; 4) the application of neuroimaging and biostatistical techniques that are unique to the research team; and (5) focus on replicability and the open science framework, including preregistration of all analyses and publicly available code. Outcomes from this project will have the potential to provide novel neurobiological targets for medication development, as well as alcohol preventions and interventions informed by neuroscience. We will also take the first steps towards the establishment of a larger international consortium of longitudinal cohort studies focused on the impact of alcohol use on brain health across the lifespan.